Vishwakarma / Sharpe / Shi Stem Cell Biology and Tissue Engineering in Dental Sciences

1. Auflage 2014
ISBN: 978-0-12-397778-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 932 Seiten

Stem Cell Biology and Tissue Engineering in Dental Sciences bridges the gap left by many tissue engineering and stem cell biology titles to highlight the significance of translational research in this field in the medical sciences. It compiles basic developmental biology with keen focus on cell and matrix biology, stem cells with relevance to tissue engineering biomaterials including nanotechnology and current applications in various disciplines of dental sciences; viz., periodontology, endodontics, oral & craniofacial surgery, dental implantology, orthodontics & dentofacial orthopedics, organ engineering and transplant medicine. In addition, it covers research ethics, laws and industrial pitfalls that are of particular importance for the future production of tissue constructs. Tissue Engineering is an interdisciplinary field of biomedical research, which combines life, engineering and materials sciences, to progress the maintenance, repair and replacement of diseased and damaged tissues. This ever-emerging area of research applies an understanding of normal tissue physiology to develop novel biomaterial, acellular and cell-based technologies for clinical and non-clinical applications. As evident in numerous medical disciplines, tissue engineering strategies are now being increasingly developed and evaluated as potential routine therapies for oral and craniofacial tissue repair and regeneration. - Diligently covers all the aspects related to stem cell biology and tissue engineering in dental sciences: basic science, research, clinical application and commercialization - Provides detailed descriptions of new, modern technologies, fabrication techniques employed in the fields of stem cells, biomaterials and tissue engineering research including details of latest advances in nanotechnology - Includes a description of stem cell biology with details focused on oral and craniofacial stem cells and their potential research application throughout medicine - Print book is available and black and white, and the ebook is in full color

Autoren/Hrsg.

Vishwakarma, Ajaykumar

Sharpe, Paul

Shi, Songtao

Ramalingam, Murugan

Inhaltsverzeichnis

1;Front Cover;1
2;Stem Cell Biology and Tissue Engineering in Dental Sciences;4
3;Copyright;5
4;Contents;6
5;List of Contributors;24
6;Foreword;32
7;Chapter 1: An Introduction to Stem Cell Biology and Tissue Engineering;34
7.1;1.1. Introduction;34
7.2;1.2. The emergence of Tissue Engineering and regenerative medicine;35
7.3;1.3. Research themes underlying Tissue Engineering technology;37
7.3.1;1.3.1. Cells;37
7.3.2;1.3.2. Biomaterial Scaffolds;39
7.3.3;1.3.3. Tissue-Inducing Factors;40
7.3.4;1.3.4. Devices and Systems;41
7.4;1.4. Stem cell-based therapy;41
7.4.1;1.4.1. Pure Stem Cell Therapy;42
7.4.2;1.4.2. Scaffold-Based Stem Cell Therapy;42
7.5;1.5. Translational Tissue Engineering;43
7.6;1.6. Conclusion;44
7.7;References;44
8;Part I: Developmental Biology: A Blueprint for Tissue Engineering;48
8.1;Chapter 2: Developmentally Inspired Regenerative Organ Engineering: Tooth as a Model ;50
8.1.1;2.1. Introduction;50
8.1.2;2.2. Understanding generation for regeneration strategies: a tooth model;50
8.1.3;2.3. Epithelial-mesenchymal interactions during odontogenesis;51
8.1.4;2.4. ECM and mechanical forces as regulators of organogenesis;53
8.1.5;2.5. Engineering approaches for tooth organ regeneration;53
8.1.6;2.6. Conclusion;55
8.1.7;References;56
8.2;Chapter 3: Extracellular Matrix Molecules;58
8.2.1;3.1. Introduction;58
8.2.1.1;3.1.1. Overview;58
8.2.1.2;3.1.2. Extracellular Matrix Proteins;59
8.2.1.3;3.1.3. Crosslinking;60
8.2.2;3.2. Collagens;60
8.2.2.1;3.2.1. Collagen Biosynthesis and Processing;61
8.2.2.2;3.2.2. Fibril-Forming Collagens;61
8.2.2.2.1;3.2.2.1. Biomineralization;63
8.2.2.3;3.2.3. Fibril-Associated Collagens (FACITs);63
8.2.2.4;3.2.4. Network-Forming Collagens;63
8.2.2.5;3.2.5. Anchoring Fibrils;64
8.2.2.6;3.2.6. Other Collagens;64
8.2.2.7;3.2.7. Collagenopathies;64
8.2.2.7.1;3.2.7.1. Osteogenesis Imperfecta (OI);64
8.2.2.7.2;3.2.7.2. Ehlers-Danlos Syndrome;66
8.2.2.7.3;3.2.7.3. Skeletal Dysplasias and Chondrodysplasias;66
8.2.2.7.4;3.2.7.4. Other Collagenopathies;66
8.2.3;3.3. Glycoproteins;67
8.2.3.1;3.3.1. Fibronectin;67
8.2.3.2;3.3.2. Fibrillins and Latent TGF-ß-Binding Proteins (LTBPs);67
8.2.3.2.1;3.3.2.1. Structural and Functional Properties of Fibrillins and LTBPs;67
8.2.3.2.2;3.3.2.2. Fibrillinopathies;68
8.2.3.3;3.3.3. Fibulins;69
8.2.3.4;3.3.4. Other Glycoproteins;69
8.2.3.4.1;3.3.4.1. Tenascin;69
8.2.3.4.2;3.3.4.2. The Small Integrin-Binding Ligand N-Linked Glycoproteins (SIBLINGs);69
8.2.3.4.3;3.3.4.3. Thrombospondins;70
8.2.4;3.4. Elastin and Elastic Fibers;70
8.2.4.1;3.4.1. Elastic Fiber Assembly;70
8.2.4.2;3.4.2. Elastin-Associated Pathologies;70
8.2.5;3.5. Basement Membranes;70
8.2.5.1;3.5.1. Laminins;71
8.2.5.2;3.5.2. Collagen Type IV;71
8.2.5.3;3.5.3. Basement Membrane Proteoglycans;71
8.2.5.4;3.5.4. Basement Membrane-Associated Pathologies;72
8.2.6;3.6. Proteoglycans and Glycosaminoglycans;73
8.2.6.1;3.6.1. Glycosaminoglycans;73
8.2.6.2;3.6.2. Proteoglycans;74
8.2.6.2.1;3.6.2.1. Cell Surface Proteoglycans;74
8.2.6.2.2;3.6.2.2. Modular Proteoglycans;74
8.2.6.2.3;3.6.2.3. Small Leucine Rich Proteoglycans (SLRPs);74
8.2.7;3.7. Concluding Remarks;75
8.2.8;Acknowledgments;75
8.2.9;Abbreviations;75
8.2.10;References;76
8.3;Chapter 4: Cell-Matrix Interactions and Signal Transduction;80
8.3.1;4.1. Introduction;80
8.3.1.1;4.1.1. The First Evidence that Matrices Change Cell Behavior;80
8.3.1.2;4.1.2. Integrin and Non-Integrin Receptor Discovery;82
8.3.2;4.2. Receptors;83
8.3.2.1;4.2.1. Integrins: Mediators of Cell-Matrix Interactions;83
8.3.2.1.1;4.2.1.1. Integrin a Subunits;83
8.3.2.1.2;4.2.1.2. Integrin ß Subunits;83
8.3.2.2;4.2.2. Non-Integrin Receptors for ECM Molecules;84
8.3.2.2.1;4.2.2.1. Syndecans;84
8.3.2.2.2;4.2.2.2. Laminin Receptor;84
8.3.2.2.3;4.2.2.3. Discoidin Domain Receptors;84
8.3.2.2.4;4.2.2.4. Leukocyte-Associated Immunoglobulin-Like Receptor-1;84
8.3.2.2.5;4.2.2.5. Glycoprotein VI;84
8.3.3;4.3. Cell-Matrix Signaling Transduction;85
8.3.3.1;4.3.1. Integrin-Mediated Cell-Matrix Signal Transduction;85
8.3.3.2;4.3.2. Crosstalk Between Integrin and Other Surface Receptor Pathways;86
8.3.4;4.4. Control Over Cell-Matrix Interactions;87
8.3.4.1;4.4.1. Control over Cell-Matrix Interaction Through Matrix Mechanical Forces;87
8.3.4.2;4.4.2. Control over Cell-Matrix Interaction Through Matrix Topography;88
8.3.4.3;4.4.3. Regulation of ECM Remodeling by Cell-Matrix Interactions;89
8.3.5;4.5. Cell-Matrix Interactions and Signal Transductions Viewed in Three Dimensions;90
8.3.6;4.6. Conclusion;91
8.3.7;References;91
8.4;Chapter 5: Cell Adhesion and Movement;94
8.4.1;5.1. Overview;94
8.4.2;5.2. Cell Adhesions;94
8.4.2.1;5.2.1. Cell Adhesions to Matrix;94
8.4.2.1.1;5.2.1.1. Focal Complexes;95
8.4.2.1.2;5.2.1.2. Focal Adhesions;95
8.4.2.1.3;5.2.1.3. Fibrillar Adhesions;96
8.4.2.1.4;5.2.1.4. Podosomes;96
8.4.2.1.5;5.2.1.5. Invadopodia;96
8.4.2.1.6;5.2.1.6. Non-Integrin-Mediated Adhesions to Matrix;96
8.4.2.1.7;5.2.1.7. Adhesions in Three-Dimensional (3D) Spaces;96
8.4.2.2;5.2.2. Cell Adhesions to Other Cells;96
8.4.2.2.1;5.2.2.1. Adherens Junctions;97
8.4.2.2.2;5.2.2.2. Tight Junctions;98
8.4.2.2.3;5.2.2.3. Gap Junctions;98
8.4.2.2.4;5.2.2.4. Desmosomes;98
8.4.2.2.5;5.2.2.5. Hemidesmosomes;98
8.4.3;5.3. Cell Movements;98
8.4.3.1;5.3.1. Single Cell Migration;98
8.4.3.1.1;5.3.1.1. Chemotaxis;99
8.4.3.1.2;5.3.1.2. Haptotaxis;99
8.4.3.1.3;5.3.1.3. Durotaxis;99
8.4.3.2;5.3.2. Collective Migration;100
8.4.3.2.1;5.3.2.1. Sheet Migration;100
8.4.3.2.2;5.3.2.2. Cell-Cell Contact-Guided Migration;101
8.4.3.2.3;5.3.2.3. Tailgating Migration;101
8.4.4;5.4. Conclusion;101
8.4.5;Abbreviations;101
8.4.6;References;101
9;Part II: In Vitro Regulation of Cell Behaviour and Tissue Development;106
9.1;Chapter 6: Genetic Manipulation Via Gene Transfer;108
9.1.1;6.1. Introduction to Basic Biology of Gene Transfer;108
9.1.2;6.2. Gene Transfer Methodologies;109
9.1.2.1;6.2.1. Specific Gene Delivery Approaches;110
9.1.2.1.1;6.2.1.1. Viral Vectors;110
9.1.2.1.2;6.2.1.2. Nanoparticles;110
9.1.2.1.3;6.2.1.3. Naked DNA Entry Through Membrane Disruption;110
9.1.2.2;6.2.2. Gene Delivery Considerations;111
9.1.2.2.1;6.2.2.1. Endosomal Escape Mediated by Viral Vectors and Nanoparticles;111
9.1.2.2.2;6.2.2.2. Cytoplasmic Trafficking of Genetic Payload;111
9.1.2.2.3;6.2.2.3. Nuclear Import and Fate of Genetic Payload;111
9.1.2.2.4;6.2.2.4. Matching Vector and Target;112
9.1.3;6.3. Host Response to Gene Transfer;112
9.1.3.1;6.3.1. Classical Anti-Viral Response to Viral-Mediated Gene Transfer;112
9.1.3.2;6.3.2. Intracellular Response to Gene Transfer;113
9.1.3.3;6.3.3. Implications for Human Gene Therapy;113
9.1.4;6.4. Examples of Successful Genetic Manipulation via in Vivo Gene Transfer;113
9.1.4.1;6.4.1. Pre-Clinical Ex Vivo and In Vivo Gene Transfer Strategies;113
9.1.4.2;6.4.2. Future Potential Approaches to Gene Therapy Currently at Earlier Stages of Development;114
9.1.4.3;6.4.3. Limitations of Pre-Clinical Studies;115
9.1.5;6.5. Pathway to Clinical Implementation of Therapeutic Gene Transfer;115
9.1.6;6.6. Conclusion;116
9.1.7;References;116
9.2;Chapter 7: Growth Factors: Biochemical Signals for Tissue Engineering;118
9.2.1;7.1. Growth Factors and Signal Transduction;118
9.2.2;7.2. Growth Factors and Signaling in Tissue Development;119
9.2.2.1;7.2.1. Tissue Interactions in Tooth Development;119
9.2.2.2;7.2.2. Signaling Networks in Dental Epithelium;120
9.2.2.3;7.2.3. Signaling Networks in Dental Mesenchyme;123
9.2.2.4;7.2.4. Signaling Networks Involved in Determining Tooth Number;123
9.2.3;7.3. Overview of the Signaling Pathways;124
9.2.3.1;7.3.1. BMP Signaling Pathway;124
9.2.3.2;7.3.2. FGF Signaling Pathway;125
9.2.3.3;7.3.3. Hedgehog Pathway;125
9.2.3.4;7.3.4. Wnt Signaling Pathway;126
9.2.4;7.4. Conclusion;127
9.2.5;Acknowledgments;127
9.2.6;References;127
9.3;Chapter 8: Mechanical and Physical Regulation of Cell Behavior;132
9.3.1;8.1. Introduction;132
9.3.1.1;8.1.1. Key Concepts;133
9.3.2;8.2. Tensile Stretch Regulation of Cell Behavior;133
9.3.2.1;8.2.1. Stretching in Two-Dimensional Environments;134
9.3.2.2;8.2.2. Stretching in Three-Dimensional Environments;136
9.3.3;8.3. Compression/Pressurization Regulation of Cell Behavior;137
9.3.4;8.4. Fluid Flow Regulation of Cell Behavior;140
9.3.4.1;8.4.1. Two-Dimensional Macro Fluid Flow;140
9.3.4.2;8.4.2. Three-Dimensional Macro Fluid Flow;141
9.3.4.3;8.4.3. Microfluidics;142
9.3.5;8.5. Alternative Stimulation Techniques;143
9.3.6;8.6. Synergy of Physical Cues and Other Factors;144
9.3.7;8.7. Conclusion;144
9.3.8;Abbreviations;145
9.3.9;References;145
9.4;Chapter 9: Bioreactor Technology for Engineering Craniofacial Tissues;150
9.4.1;9.1. Introduction: Rationale for Using Bioreactors in Stem Cell-Based Tissue Engineering;150
9.4.1.1;9.1.1. Key Concepts;151
9.4.2;9.2. Principles of Bioreactor Design;151
9.4.2.1;9.2.1. Environmental Control;151
9.4.2.2;9.2.2. Mass Transport;152
9.4.2.3;9.2.3. Sterility;152
9.4.2.4;9.2.4. Cell Seeding;152
9.4.2.5;9.2.5. Common Bioreactor Designs;153
9.4.2.5.1;9.2.5.1. Continuous Stirred-Tank Bioreactors;153
9.4.2.5.2;9.2.5.2. Rotating Wall Vessel Bioreactors;153
9.4.2.5.3;9.2.5.3. Perfusion Bioreactors;153
9.4.2.5.4;9.2.5.4. Customized Bioreactor Designs;153
9.4.3;9.3. Case Studies;154
9.4.3.1;9.3.1. Perfusion Bioreactors for Engineering Anatomically Shaped TMJ Bone Grafts;154
9.4.3.2;9.3.2. Bioreactors for Meniscus Tissue Engineering;155
9.4.3.2.1;9.3.2.1. Rotating Wall Bioreactor for TMJ Disc;156
9.4.3.2.2;9.3.2.2. Tension-Compression Bioreactor for Meniscus Engineering;157
9.4.3.3;9.3.3. Bioreactors for Engineering Aligned Periodontal Ligament Tissues;157
9.4.4;9.4. Future Perspectives;159
9.4.4.1;9.4.1. Bioreactors for Composite Tissues;159
9.4.4.2;9.4.2. Tissue Engineering Bioreactors for Clinical Application;160
9.4.5;9.5. Conclusion;161
9.4.6;References;161
10;Part III: Biomaterials in Tissue Engineering;164
10.1;Chapter 10: Considerations on Designing Scaffold for Tissue Engineering;166
10.1.1;10.1. Introduction to Scaffold-Based Tissue Engineering;166
10.1.1.1;10.2. Importance of Scaffolds in Tissue Engineering and Their Role;167
10.1.2;10.3. Scaffold Designing Criteria;168
10.1.2.1;10.3.1. Scaffold Properties to Consider;168
10.1.2.2;10.3.2. Selection of Biomaterials;168
10.1.3;10.4. Cell Matrix (scaffold) Interactions;173
10.1.4;10.5. Fabrication Techniques for Three-Dimensional Scaffolds;174
10.1.4.1;10.5.1. Conventional Methods;174
10.1.4.1.1;10.5.1.1. Solvent-Casting Particulate Leaching;174
10.1.4.1.2;10.5.1.2. Gas Foaming;175
10.1.4.1.3;10.5.1.3. Fiber Meshes/Fiber Bonding;175
10.1.4.1.4;10.5.1.4. Phase Separation;175
10.1.4.1.5;10.5.1.5. Melt Molding;175
10.1.4.1.6;10.5.1.6. Emulsion Freeze Drying;175
10.1.4.1.7;10.5.1.7. Solution Casting;175
10.1.4.2;10.5.2. Solid Free Fabrication Methods;175
10.1.4.2.1;10.5.2.1. Stereolithography and Selective Laser Sintering;175
10.1.4.2.2;10.5.2.2. Three-Dimensional Printing;176
10.1.4.2.3;10.5.2.3. Microsyringe Deposition;176
10.1.4.3;10.5.3. Microfabrication Techniques Based on Physical Properties;176
10.1.4.3.1;10.5.3.1. Microphase Separation;176
10.1.4.3.2;10.5.3.2. Self-Assembly;176
10.1.4.4;10.5.4. Hybrid Scaffolds;177
10.1.4.5;10.5.5. Nanofabricated Scaffolds;177
10.1.4.5.1;10.5.5.1. Electrospinning;177
10.1.4.5.2;10.5.5.2. Colloidal Adsorption;178
10.1.5;10.6. Conclusion and Future Trends;178
10.1.6;Abbreviations;179
10.1.7;References;179
10.2;Chapter 11: Polymeric Biomaterials as Tissue Scaffolds;182
10.2.1;11.1. Introduction;182
10.2.1.1;11.1.1. Natural Polymers;182
10.2.1.2;11.1.2. Synthetic Polymers;183
10.2.2;11.2. Non-Biodegradable Synthetic Biomaterials;183
10.2.2.1;11.2.1. Ceramics and Bioactive Glass;183
10.2.3;11.3. Degradable Synthetic Biomaterials;183
10.2.3.1;11.3.1. Polyesters;183
10.2.3.1.1;11.3.1.1. Poly(Glycolide);184
10.2.3.1.2;11.3.1.2. Poly(Lactide);184
10.2.3.1.3;11.3.1.3. Poly(Caprolactone);185
10.2.3.1.4;11.3.1.4. Poly(Trimethylene Carbonate);185
10.2.3.2;11.3.2. Poly (Ether-Ester);185
10.2.3.2.1;11.3.2.1. Poly(Dioxanone);185
10.2.3.3;11.3.3. Poly(Ethylene Glycol);186
10.2.4;11.4. Bone Tissue Engineering in the Oral Cavity;186
10.2.4.1;11.4.1. Biomaterials for Bone Tissue Engineering;186
10.2.5;11.5. Tissue Engineering of the Gingiva and Other Soft Tissues;187
10.2.5.1;11.5.1. Epidermal Replacements;187
10.2.5.2;11.5.2. Dermal Replacements;188
10.2.6;11.6. Dental Nerve Injuries;189
10.2.6.1;11.6.1. Scaffolds for Nerve Tissue Engineering;189
10.2.7;11.7. Conclusion;191
10.2.8;Abbreviations;191
10.2.9;References;191
10.3;Chapter 12: Ceramic Biomaterials as Tissue Scaffolds;196
10.3.1;12.1. Introduction to Bioceramic Scaffolds;196
10.3.2;12.2. Calcium Phosphates;197
10.3.2.1;12.2.1. Preparation of Hydroxyapatite;198
10.3.2.2;12.2.2. Wet Methods;198
10.3.2.3;12.2.3. Dry Methods;199
10.3.2.4;12.2.4. Hydrothermal Methods;199
10.3.2.5;12.2.5. Biphasic Ceramics;199
10.3.3;12.3. Bioactive Glasses and Glass-Ceramics;199
10.3.3.1;12.3.1. Composition of Bioactive Glasses and Glass-Ceramics;199
10.3.3.2;12.3.2. Fabrication of Bioactive Glass and Glass-Ceramics;201
10.3.3.3;12.3.3. Properties of Bioactive Glass and Glass-Ceramics;201
10.3.3.4;12.3.4. Surface Reaction and Tissue Bonding;201
10.3.3.5;12.3.5. Clinical Applications of Bioactive Glass and Glass-Ceramics;202
10.3.4;12.4. Processing Methods for Scaffold Production;202
10.3.4.1;12.4.1. Foam Templating Methods;202
10.3.4.2;12.4.2. Leaching and Burnout Methods;203
10.3.4.3;12.4.3. Additive Layer Manufacturing;203
10.3.5;12.5. Naturally-Derived Implant Materials;203
10.3.5.1;12.5.1. Deproteinized Bone;203
10.3.5.2;12.5.2. Thermally-Treated Bovine Bone;204
10.3.6;12.6. Interaction of Bioceramics with Cells;204
10.3.7;12.7. Summary;204
10.3.8;References;204
10.4;Chapter 13: Gradient Biomaterials as Tissue Scaffolds;208
10.4.1;13.1. Introduction;208
10.4.2;13.2. The Concept of Gradient Biomaterials;211
10.4.2.1;13.2.1. Physical Gradients;211
10.4.2.2;13.2.2. Gradients of Surface Properties;211
10.4.2.3;13.2.3. Pore Size/Porosity Gradients;212
10.4.2.4;13.2.4. Substrate Stiffness Gradients;213
10.4.3;13.3. Chemical/Biological Gradients;214
10.4.3.1;13.3.1. Immobilized Factor Gradients;214
10.4.3.2;13.3.2. Soluble Gradients;215
10.4.4;13.4. Conclusion;216
10.4.5;Abbreviations;216
10.4.6;References;216
10.5;Chapter 14: Surface Functionalization of Biomaterials;220
10.5.1;14.1. Introduction;220
10.5.2;14.2. Responses to Biomaterial Implantation;220
10.5.3;14.3. Surface Modification Techniques;222
10.5.3.1;14.3.1. Chemically Based Methods;223
10.5.3.1.1;14.3.1.1. Surface Hydrolysis;223
10.5.3.1.2;14.3.1.2. Surface Oxidation;224
10.5.3.1.3;14.3.1.3. Aminolysis;224
10.5.3.1.4;14.3.1.4. Plasma Treatment;225
10.5.3.1.5;14.3.1.5. Surface Grafting Strategies;225
10.5.3.2;14.3.2. Physically Based Methods;226
10.5.3.2.1;14.3.2.1. Surface Adsorption;226
10.5.3.2.2;14.3.2.2. Entrapment;226
10.5.3.2.3;14.3.2.3. Self-Assembled Monolayers;226
10.5.3.2.4;14.3.2.4. Electrostatic Layer-by-Layer Deposition;227
10.5.4;14.4. Anti-Fouling Surface Modification Strategies;228
10.5.4.1;14.4.1. Poly(Ethylene Glycol) (PEG);228
10.5.4.2;14.4.2. Polysaccharides;229
10.5.4.3;14.4.3. Zwitterionic Polymers;230
10.5.5;14.5. Biomimetic Surface Modification Strategies;230
10.5.5.1;14.5.1. Proteins and Peptides;230
10.5.5.2;14.5.2. Surface Biomineralization;231
10.5.6;14.6. Bioactive Surface Modification Strategies;232
10.5.7;14.7. Hybrid Strategies;232
10.5.8;14.8. Challenges in Three-Dimensional (3D) Surface Modification;233
10.5.9;Abbreviations;233
10.5.10;References;233
10.6;Chapter 15: Microfabrication and Nanofabrication Techniques;240
10.6.1;15.1. Introduction;240
10.6.2;15.2. Delivery of Soluble Factors Using Micro- and Nanofabrication Techniques;241
10.6.3;15.3. Microfabrication and Nanofabrication of Scaffolds;242
10.6.3.1;15.3.1. Vascular Network and Nerve Regeneration within Scaffolds;243
10.6.4;15.4. Micro- and Nanofabrication Techniques for Direct Fabrication of Cell-Laden Constructs;247
10.6.5;15.5. Elucidation of Stem Cell Biology Using Micro- and Nanofabrication Techniques;247
10.6.6;15.6. Concluding Remarks and Future Directions;248
10.6.7;Acknowledgments;249
10.6.8;Abbreviations;249
10.6.9;References;249
10.7;Chapter 16: Nanobiomaterials for Tissue Engineering Applications;254
10.7.1;16.1. Introduction;254
10.7.2;16.2. Two-Dimensional Nanotechnology for Dental Application;255
10.7.2.1;16.2.1. Nanolithography;255
10.7.2.1.1;16.2.1.1. Hot Embossing Imprint Lithography;256
10.7.2.2;16.2.2. Chemical Etching;256
10.7.2.3;16.2.3. Grit Blasting;257
10.7.3;16.3. Three-Dimensional Nanotechnology for Dental Applications;258
10.7.3.1;16.3.1. Nanohydroxyapatite;258
10.7.3.2;16.3.2. Nanofibers;260
10.7.3.2.1;16.3.2.1. Electrospinning;260
10.7.3.2.2;16.3.2.2. Self-Assembled Nanomaterials;260
10.7.3.3;16.3.3. Carbon Nanotubes;261
10.7.4;16.4. Nanoparticles for Drug Delivery;262
10.7.4.1;16.4.1. Nanobiomaterial and Cellular Interactions;263
10.7.5;16.5. Conclusions;264
10.7.6;Acronyms and Abbreviations;264
10.7.7;References;264
11;Part IV: Oral and Craniofacial Stem Cells for Tissue Engineering;268
11.1;Chapter 17: The Basic Principles of Stem Cells;270
11.1.1;17.1. Introduction to Stem Cells;270
11.1.2;17.2. A Brief History of Stem Cell Research;271
11.1.3;17.3. Characterization of Stem Cells;271
11.1.3.1;17.3.1. Origin of Stem Cells;271
11.1.4;17.4. Biological Properties of Stem Cells;272
11.1.4.1;17.4.1. Self-Renewal;272
11.1.4.2;17.4.2. Extensive Proliferative Capacity;273
11.1.4.3;17.4.3. Differentiation Potential;274
11.1.4.4;17.4.4. Stem Cell Plasticity;275
11.1.4.5;17.4.5. Stem Cell Resistance and Quiescence;276
11.1.5;17.5. Stem Cell Niche;277
11.1.6;17.6. Conclusion;278
11.1.7;Acknowledgment;278
11.1.8;Abbreviations;278
11.1.9;References;279
11.2;Chapter 18: Embryonic Versus Adult Stem Cells;282
11.2.1;18.1. Introduction;282
11.2.2;18.2. Embryonic Stem Cells;282
11.2.2.1;18.2.1. Definition;282
11.2.2.2;18.2.2. Origin and Derivation;282
11.2.2.3;18.2.3. Differentiation of ESCs In Vivo Versus In Vitro;283
11.2.2.4;18.2.4. Validation of Stem Cell Populations;283
11.2.2.4.1;18.2.4.1. Stem Cell Markers;283
11.2.2.4.2;18.2.4.2. Defining Characteristics of ESCs;283
11.2.2.4.2.1;18.2.4.2.1. Embryoid Body (EB) and Teratoma Formation in Mice;283
11.2.2.4.2.2;18.2.4.2.2. Derivation of Chimeric Offspring In Vivo and Tetraploid Complementation;283
11.2.2.5;18.2.5. Signaling Regulation in ESCs;283
11.2.2.6;18.2.6. ESC Culture Dependence on Growth Factors;284
11.2.2.7;18.2.7. iPS Cells;284
11.2.2.8;18.2.8. Applications of ESCs;285
11.2.3;18.3. Adult Stem Cells;285
11.2.3.1;18.3.1. Definition;285
11.2.3.2;18.3.2. Types of Adult Stem Cells and Their Markers;285
11.2.3.2.1;18.3.2.1. Hematopoietic Stem Cells;285
11.2.3.2.2;18.3.2.2. Mesenchymal Stem Cells;286
11.2.3.2.3;18.3.2.3. Intestinal Stem Cells;287
11.2.3.2.4;18.3.2.4. Neuronal Stem Cells;288
11.2.3.2.5;18.3.2.5. Stem Cells of the Epidermis and Hair Follicle;288
11.2.3.2.5.1;18.3.2.5.1. Epidermal Stem Cells;288
11.2.3.2.5.2;18.3.2.5.2. Hair Follicle Stem Cells;289
11.2.3.2.5.3;18.3.2.5.3. Sebaceous Gland Stem Cells;290
11.2.3.2.5.4;18.3.2.5.4. Dermal Papilla;290
11.2.3.2.6;18.3.2.6. Other Adult Stem Cell Populations;290
11.2.4;18.4. Applications of Adult Stem Cells;291
11.2.5;18.5. Conclusion;291
11.2.6;Abbreviations;292
11.2.7;References;292
11.3;Chapter 19: Dental Epithelial Stem;296
11.3.1;19.1. Introduction;296
11.3.2;19.2. Differentiation of Epithelial Cell Lineages in the Developing Tooth;296
11.3.3;19.3. Epithelial Stem Cells in the Continuously Growing Mouse Incisor;297
11.3.4;19.4. Epithelial Stem and Progenitor Cells for Tooth Replacement;300
11.3.5;19.5. Dental Lamina as the Origin of Epithelial Cells in Teeth;301
11.3.6;19.6. Conclusion;301
11.3.7;Abbreviations;302
11.3.8;References;302
11.4;Chapter 20: Dental Follicle Stem Cells;304
11.4.1;20.1. Introduction;304
11.4.2;20.2. Dental Follicle Cell Culture;305
11.4.3;20.3. Stem Cells of the Human Dental Follicle;306
11.4.3.1;20.3.1. Isolation of Multipotent Cells from the Coronal Human DF;306
11.4.3.1.1;20.3.1.1. The Migration Capacity of DFCs;306
11.4.3.1.2;20.3.1.2. The Regulation of the Differentiation of DFCs;306
11.4.3.2;20.3.2. The Periapical Follicle Stem Cells (PAFSCs);307
11.4.3.3;20.3.3. Follicle-Derived Embryonic Neural Crest Stem Cells (FENCSCs);308
11.4.4;20.4. Dental Follicle Cells for Regenerative Dentistry;308
11.4.5;20.5. Conclusion;309
11.4.6;References;309
11.5;Chapter 21: Dental Pulp Stem Cells;312
11.5.1;21.1. Introduction;312
11.5.2;21.2. Human Dental Pulp-Derived Mesenchymal Stem-Like Cells;313
11.5.2.1;21.2.1. Identification;313
11.5.2.2;21.2.2. Characterization and Origin;313
11.5.2.3;21.2.3. Growth Potential;315
11.5.3;21.3. Properties of Stem Cell Populations from Dental Pulp Tissue;315
11.5.3.1;21.3.1. Regenerative Potential of Mineralized Tissues;315
11.5.3.2;21.3.2. Immunomodulatory Properties;317
11.5.3.3;21.3.3. Neural Tissue Regenerative Potential;317
11.5.3.4;21.3.4. Dental Pulp-Derived Inducible Pluripotent Stem Cells;318
11.5.4;21.4. Conclusion;318
11.5.5;References;318
11.6;Chapter 22: Periodontal Ligament Stem Cells;324
11.6.1;22.1. Introduction;324
11.6.2;22.2. Periodontal Ligament Stem Cells (PDLSCs);324
11.6.2.1;22.2.1. Identification;324
11.6.2.2;22.2.2. Characterization and Origin;324
11.6.2.3;22.2.3. Growth Potential;325
11.6.3;22.3. Induced Pluripotent Stem Cells from Periodontal Ligaments;325
11.6.3.1;22.3.1. Regaining Pluripotent Stem Cell Properties;325
11.6.3.2;22.3.2. Dental Originated Pluripotent Stem Cells;326
11.6.3.3;22.3.3. Application of iPSCs to Dental Regeneration;326
11.6.4;22.4. Epithelial Stem Cells from Periodontal Ligament;326
11.6.4.1;22.4.1. Hertwig’s Epithelial Root Sheath and the Epithelial Cell Rests of Malassez (HERS/ERM);326
11.6.4.2;22.4.2. Epithelial Stem Cells in Periodontal Ligaments and ERM;326
11.6.5;22.5. Clinical Regeneration Properties and Potential of PDLSCs;327
11.6.5.1;22.5.1. Clinical Regeneration of Periodontium;327
11.6.5.2;22.5.2. Xeno-Free In Vitro Culture;327
11.6.5.3;22.5.3. Interaction with Multiple Tissue Structure;328
11.6.5.4;Abbreviations;328
11.6.6;References;328
11.7;Chapter 23: Oral Mucosal Progenitor Cells;330
11.7.1;23.1. Introduction;330
11.7.1.1;23.1.1. The Oral Mucosa;330
11.7.1.2;23.1.2. Distinct Tissue Repair Properties of the Oral Mucosa;330
11.7.2;23.2. Geno- and Phenotypic Characteristics of Oral Mucosal Fibroblasts;331
11.7.3;23.3. Oral Mucosa Progenitor Cells;331
11.7.3.1;23.3.1. Characterization of Oral Mucosa Lamina Propria Progenitor Cells;331
11.7.3.2;23.3.2. Oral Progenitors as a Source of iPSCs;333
11.7.3.3;23.3.3. Oral Mucosal Progenitors as Potent Immunosuppressive Cells;333
11.7.3.3.1;23.3.3.1. MSCs and the Immune System;333
11.7.3.3.2;23.3.3.2. Immunosuppressive Soluble Factors;333
11.7.3.3.3;23.3.3.3. The Immunomodulatory Potential of Oral Progenitors;333
11.7.4;23.4. Conclusion;336
11.7.5;Acknowledgments;337
11.7.6;Abbreviations;337
11.7.7;References;337
11.8;Chapter 24: Oral Mucosal Stem Cells: Identification, Characterization, and Clinical and Disease Implications ;340
11.8.1;24.1. Introduction;340
11.8.2;24.2. Molecular and Phenotypic Markers for KSC Identification;341
11.8.2.1;24.2.1. Adult Hair Follicle KSC Markers;341
11.8.2.2;24.2.2. Epidermal KSC Markers;342
11.8.2.3;24.2.3. Corneal Limbal Stem Cell Markers;342
11.8.2.4;24.2.4. OKSC Markers;342
11.8.2.5;24.2.5. Enrichment of KSCs from Primary Tissue Specimens;342
11.8.3;24.3. Generation of Keratinocytes from Pluripotent Stem Cells;343
11.8.4;24.4. Molecular Pathways Regulating KSC Stemness;343
11.8.4.1;24.4.1. Notch Signaling Pathway;343
11.8.4.2;24.4.2. Wnt Signaling Pathway;343
11.8.4.3;24.4.3. TGF- ß /BMP Signaling Pathway;343
11.8.5;24.5. Epithelial Tissue Engineering Using OKSCs;344
11.8.5.1;24.5.1. Enhanced Regeneration Capacity of OKSCs;344
11.8.5.1.1;24.5.1.1. Wound Healing Example;344
11.8.5.2;24.5.2. Oral Mucosal Graft Transplantation;345
11.8.5.3;24.5.3. OKSC Scaffold Transplantation in Ocular Reconstruction;345
11.8.6;24.6. Control of Replication, Senescence, and Differentiation of Oral Keratinocytes;345
11.8.6.1;24.6.1. Intrinsic Model of Cellular Senescence;346
11.8.6.1.1;24.6.1.1. Dependence on Telomere Status;346
11.8.6.2;24.6.2. Extrinsic Model of Senescence;346
11.8.6.2.1;24.6.2.1. Dependence on Environmental Factors;346
11.8.6.3;24.6.3. Control of Keratinocyte Differentiation;347
11.8.6.3.1;24.6.3.1. Grainyhead-Like 2 Is the Master Regulator of Keratinocyte Proliferation and Differentiation;347
11.8.7;24.7. Mechanisms Involving Cellular Immortalization of Oral Mucosal Keratinocytes;349
11.8.8;24.8. Relevance of KSCS for Oral Carcinogenesis;349
11.8.9;Acknowledgments;351
11.8.10;Abbreviations;351
11.8.11;References;351
11.9;Chapter 25: Optimization of Stem Cell Expansion, Storage, and Distribution;356
11.9.1;25.1. Introduction;356
11.9.2;25.2. Key Concepts;356
11.9.3;25.3. Optimization of Stem Cell Expansion Processes;357
11.9.3.1;25.3.1. Recent Developments in Somatic Stem Cell Culture;357
11.9.3.1.1;25.3.1.1. Optimal Culture and Induction Protocols;357
11.9.3.1.2;25.3.1.2. Animal-Free Culture;357
11.9.3.1.3;25.3.1.3. Novel Culture Technologies;358
11.9.3.1.4;25.3.1.4. Automated Cell Culture Systems;359
11.9.3.2;25.3.2. Expansion of Bone Marrow Stromal Cells for Bone Tissue Engineering;360
11.9.3.2.1;25.3.2.1. Consideration of BMSCs Expansion for Bone Tissue Engineering;360
11.9.3.2.2;25.3.2.2. Safety Concerns of BMSCs in Clinical Application;360
11.9.3.3;25.3.3. Procedures for Seeding Cells onto Scaffolds;361
11.9.4;25.4. Development of Cell Storage Technologies;361
11.9.4.1;25.4.1. Cryopreservation of Cultured Cells;361
11.9.4.2;25.4.2. Novel Technological Developments in Cryopreservation;361
11.9.4.3;25.4.3. Considerations for the Cryopreservation of Tissue-Engineered Products;361
11.9.5;25.5. Distribution of Tissue-Engineered Products;362
11.9.5.1;25.5.1. Conditions Required for the Transportation of Tissue-Engineered Products;362
11.9.5.2;25.5.2. Effect of Transportation on Cell Viability;362
11.9.5.3;Acronyms and Abbreviations;362
11.9.6;References;362
12;Part V: Tooth Tissue Engineering;366
12.1;Chapter 26: Development of Tooth and Associated Structures;368
12.1.1;26.1. Odontogenesis;368
12.1.1.1;26.1.1. Epithelio-Mesenchymal Origin of Dental Tissues and Embryonic Development;368
12.1.1.2;26.1.2. Determination of Odontogenic Region and Tooth Identity;368
12.1.1.3;26.1.3. Antero-Posterior Patterning;369
12.1.1.4;26.1.4. Determination of Tooth Shape and Number;369
12.1.1.5;26.1.5. Morphogenesis;369
12.1.1.6;26.1.6. Terminal Differentiation and Mineralization;369
12.1.1.6.1;26.1.6.1. Dentinogenesis;370
12.1.1.6.2;26.1.6.2. Amelogenesis;370
12.1.1.6.3;26.1.6.3. Cementogenesis;371
12.1.2;26.2. Odontogenesis and Osteogenesis;372
12.1.2.1;26.2.1. Osteogenesis;372
12.1.2.2;26.2.2. Alveolar and Jaw Bone Development;372
12.1.2.3;26.2.3. Alveolar Bone: Extracellular Matrix;375
12.1.2.4;26.2.4. Root Development and Formation of Periodontium;375
12.1.2.5;26.2.5. Failures in Odontogenesis and/or Osteogenesis;377
12.1.3;References;379
12.2;Chapter 27: Dental Stem Cells for Tooth Tissue Engineering;380
12.2.1;27.1. Introduction;380
12.2.2;27.2. Embryonic and Postnatal Tooth Bud Cells;382
12.2.3;27.3. Dental Epithelial Progenitor/Stem Cell from the Enamel Organ;382
12.2.4;27.4. Epithelial Cell Rests of Malassez (ERM);383
12.2.4.1;27.4.1. Dental Epithelial Stem Cells in the ERM;385
12.2.5;27.5. Dental Papilla Progenitor Cells;386
12.2.6;27.6. Dental Follicle Stem Cells;387
12.2.7;27.7. Dental Pulp Stem Cells;388
12.2.8;27.8. Conclusion;389
12.2.9;Acknowledgments;390
12.2.10;References;390
12.3;Chapter 28: Tooth Organ Engineering;392
12.3.1;28.1. Introduction;392
12.3.2;28.2. Tooth Organ Engineering Using Dental Embryonic Cells;392
12.3.2.1;28.2.1. Crown Morphogenesis, Epithelial Histogenesis, and Cell Differentiation;392
12.3.2.2;28.2.2. Root, Periodontium, and Bone Formation;394
12.3.2.2.1;28.2.2.1. Root Formation;394
12.3.2.2.2;28.2.2.2. Periodontium Attachment to Bone;395
12.3.2.3;28.2.3. Innervation;396
12.3.2.4;28.2.4. Fate of Engineered Teeth After Long-Term Implantation;398
12.3.3;28.3. Tooth Engineering Using Non-Dental Cells;398
12.3.3.1;28.3.1. Mesenchymal Cells;398
12.3.3.2;28.3.2. Epithelial Cells;398
12.3.4;28.4. Human Dental Stem Cells;399
12.3.5;28.5. Conclusion;399
12.3.6;Acknowledgments;399
12.3.7;References;399
13;Part VI: Tissue Engineering in Endodontics;402
13.1;Chapter 29: Biology of the Dentin-Pulp Complex;404
13.1.1;29.1. Introduction;404
13.1.2;29.2. Dentin Structure and its Biochemical Properties;404
13.1.2.1;29.2.1. Predentin;405
13.1.2.2;29.2.2. Mantle Dentin;405
13.1.2.3;29.2.3. Teritary Dentin;406
13.1.3;29.3. Components of the Dentin Extracellular Matrix;406
13.1.3.1;29.3.1. Collagen;406
13.1.3.2;29.3.2. Small Leucine-Rich Proteoglycans (SLRPs);406
13.1.3.3;29.3.3. Small Integrin-Binding Ligand N-linked Glycoproteins (SIBLINGs);407
13.1.4;29.4. Growth Factors and Cytokines within the Dentin ECM;407
13.1.5;29.5. The Dental Pulp;408
13.1.5.1;29.5.1. Biochemical Properties of the Pulp;408
13.1.5.2;29.5.2. Cellular Composition of the Pulp;409
13.1.5.2.1;29.5.2.1. Odontoblasts;409
13.1.5.2.2;29.5.2.2. Dental Pulp Stem/Progenitor Cells;409
13.1.5.3;29.5.3. Other Cells of the Pulp;410
13.1.5.4;29.5.4. Nerve Endings and Neurotransmitters;410
13.1.6;References;410
13.2;Chapter 30: Odontoblasts and Dentin Formation;412
13.2.1;30.1. Key Concepts;412
13.2.2;30.2. Odontoblast Life Cycle;413
13.2.2.1;30.2.1. From Neural Mesenchymal Cells to Aged Odontoblasts;413
13.2.2.2;30.2.2. Regulation of Odontoblast Terminal Differentiation;416
13.2.3;30.3. Primary and Secondary Dentinogenesis;417
13.2.3.1;30.3.1. Primary Dentinogenesis;417
13.2.3.1.1;30.3.1.1. Matrix Molecules Synthesis and Secretion;417
13.2.3.1.1.1;30.3.1.1.1. Collagens;418
13.2.3.1.1.2;30.3.1.1.2. Non-Collagenous Proteins;418
13.2.3.1.1.3;30.3.1.1.3. SIBLINGs;418
13.2.3.1.1.4;30.3.1.1.4. Other Non-Collagenous Proteins;419
13.2.3.1.1.5;30.3.1.1.5. Proteoglycans;419
13.2.3.1.1.6;30.3.1.1.6. Glycosaminoglycans;419
13.2.3.1.1.7;30.3.1.1.7. Matrix Metalloproteinases and Other Enzymes;419
13.2.3.1.2;30.3.1.2. Mineralization Process;419
13.2.3.2;30.3.2. Secondary Dentinogenesis;420
13.2.4;30.4. Tertiary Dentinogenesis;420
13.2.4.1;30.4.1. Reactionary Dentinogenesis;420
13.2.4.2;30.4.2. Reparative Dentinogenesis;421
13.2.5;30.5. Non-Dentinogenic Function of Odontoblasts;423
13.2.5.1;30.5.1. Odontoblasts in the Dental Pulp Immune and Inflammatory Response;423
13.2.5.2;30.5.2. Odontoblasts as Sensor Cells;424
13.2.6;30.6. Conclusion;425
13.2.7;Acknowledgment;425
13.2.8;Abbreviations;425
13.2.9;References;426
13.3;Chapter 31. Pulp Injury and Changing Trends in Treatment;430
13.3.1;31.1. Introduction;430
13.3.2;31.2. Biological Basis for Regeneration;430
13.3.3;31.3. Regeneration Versus Revascularization;433
13.3.4;31.4. Overview of Current Literature from A Tissue Engineering Perspective;433
13.3.5;31.5. Are we There Yet? Considerations of Current Clinical Protocols;434
13.3.6;Acknowledgment;434
13.3.7;References;434
13.4;Chapter 32: Cellular Signaling in Dentin Repair and Regeneration;438
13.4.1;32.1. Introduction;438
13.4.2;32.2. Microbial Signaling in Caries;438
13.4.3;32.3. Dentin-Derived Molecular Signals in Caries;440
13.4.4;32.4. Dentin-Pulp Signaling and the Inflammatory Response;441
13.4.5;32.5. Signaling in Tertiary Dentinogenesis;442
13.4.5.1;32.5.1. Reactionary and Reparative Dentinogenesis;442
13.4.5.2;32.5.2. Chemotactic Signaling of Stem/Progenitor Cell Recruitment;443
13.4.5.3;32.5.3. Signaling of Odontoblast-Like Cell Differentiation and Parallels with Tooth Development;444
13.4.5.4;32.5.4. Molecular Regulation of Odontoblast Secretory Activity;444
13.4.6;32.6. Angiogenic and Neurogenic Signaling During Repair and Regeneration;445
13.4.7;32.7. Cellular Signaling and Clinical Opportunities;445
13.4.8;References;446
13.5;Chapter 33: Tissue Engineering Strategies for Endodontic Regeneration;452
13.5.1;33.1. Introduction;452
13.5.2;33.2. Treatment of Dental Pulp Necrosis in Immature Teeth;452
13.5.3;33.3. Dental Pulp Tissue Engineering;454
13.5.3.1;33.3.1. Stem Cells in Dental Pulp Tissue Engineering;456
13.5.3.2;33.3.2. Morphogenic Signals in Dental Pulp Tissue Engineering;457
13.5.3.3;33.3.3. Injectable Scaffolds in Dental Pulp Tissue Engineering;458
13.5.4;33.4. Concluding Remarks;459
13.5.5;Abbreviations;460
13.5.6;References;460
14;Part VII: Periodontal Tissue Engineering;464
14.1;Chapter 34: Periodontium and Periodontal Disease;466
14.1.1;34.1. Introduction;466
14.1.2;34.2. Functional Anatomy of the Periodontal Tissues;467
14.1.2.1;34.2.1. Gingiva;467
14.1.2.2;34.2.2. Periodontal Ligament;468
14.1.2.3;34.2.3. Alveolar Bone;468
14.1.2.4;34.2.4. Cementum;469
14.1.2.5;34.2.5. Adaptive Changes to Occlusal Loading;469
14.1.3;34.3. Signs and Symptoms of Periodontal Diseases;470
14.1.3.1;34.3.1. Gingivitis;470
14.1.3.2;34.3.2. Periodontitis;470
14.1.3.3;34.3.3. Classification of Periodontal Diseases;471
14.1.4;34.4. Etiology of Periodontal Disease;472
14.1.4.1;34.4.1. Smoking;472
14.1.4.2;34.4.2. Genetic Factors;472
14.1.4.3;34.4.3. Systemic Diseases;473
14.1.4.4;34.4.4. Psychosocial Factors;473
14.1.5;34.5. Pathogenesis;473
14.1.5.1;34.5.1. Bacterial Factors;473
14.1.5.2;34.5.2. Host Responses;473
14.1.5.3;34.5.3. Mechanisms of Tissue Damage;474
14.1.6;34.6. Management of Periodontal Diseases;474
14.1.6.1;34.6.1. Treatment Outcomes;475
14.1.7;34.7. Conclusion;476
14.1.8;References;476
14.2;Chapter 35: Biological Aspects of Periodontal Disease;478
14.2.1;35.1. Introduction;478
14.2.2;35.2. Morphogenesis;479
14.2.2.1;35.2.1. Odontogenic Progenitors Originate from the Cranial Neural Crest;479
14.2.2.2;35.2.2. Cell Fate Decisions in the Dental Follicle: Establishing the Periodontal Tissues;480
14.2.2.3;35.2.3. The Role of Hertwig’s Epithelial Root Sheath in Tooth Root and Periodontal Development;482
14.2.2.4;35.2.4. Development and Maintenance of the Gingiva;482
14.2.3;35.3. Periodontal Wound Healing;484
14.2.3.1;35.3.1. Mechanisms of Wound Healing in the Periodontium;484
14.2.3.2;35.3.2. Morphogenesis and Wound Healing of the Periodontium: Parallels and Contrasts;486
14.2.4;35.4. Current and Future Wound Healing Strategies in the Periodontium;487
14.2.5;35.5. Conclusion;487
14.2.6;Abbreviations;487
14.2.7;References;488
14.3;Chapter 36: Periodontal Regeneration: Current Therapies ;492
14.3.1;36.1. Introduction;492
14.3.2;36.2. Bone Grafts;493
14.3.2.1;36.2.1. Autografts;493
14.3.2.2;36.2.2. Allografts;494
14.3.2.3;36.2.3. Xenografts;494
14.3.2.4;36.2.4. Alloplastic Graft;494
14.3.3;36.3. Guided Tissue Regeneration (gtr);495
14.3.4;36.4. Biologics;496
14.3.4.1;36.4.1. Platelet-Derived Growth Factor (PDGF);497
14.3.4.2;36.4.2. Bone Morphogenetic Proteins (BMP);497
14.3.4.3;36.4.3. Enamel Matrix Derivative (EMD);498
14.3.4.4;36.4.4. Fibroblast Growth Factor-2 (FGF-2);498
14.3.5;36.5. Recent Advances;498
14.3.5.1;36.5.1. Gene Therapy;498
14.3.5.2;36.5.2. Stem Cell Therapy;498
14.3.6;36.6. Summary and Conclusions;499
14.3.7;Acknowledgments;499
14.3.8;References;499
14.4;Chapter 37. Periodontal Tissue Engineering: Current Approaches and Future Therapies;504
14.4.1;37.1. Introduction;504
14.4.2;37.2. Periodontal Tissue Engineering;505
14.4.3;37.3. Stem Cells for Periodontal Tissue Engineering;505
14.4.3.1;37.3.1. Stem Cells of Dental Origin;505
14.4.3.1.1;37.3.1.1. Periodontal Ligament Stem Cells (PDLSCs);505
14.4.3.1.2;37.3.1.2. Root Apical Papilla Stem Cells;507
14.4.3.1.3;37.3.1.3. Dental Follicle Stem Cells;507
14.4.3.1.4;37.3.1.4. Stem Cells from Pulp Tissue;507
14.4.3.2;37.3.2. Stem Cells of Non-Dental Origin;508
14.4.3.2.1;37.3.2.1. Bone Marrow-Derived Mesenchymal Stem Cells;508
14.4.3.2.2;37.3.2.2. Adipose-Derived Stem Cells;508
14.4.3.2.3;37.3.2.3. Embryonic Stem Cells/Induced Pluripotent Stem Cells;508
14.4.4;37.4. Cell Therapy for Periodontal Tissue Engineering;509
14.4.4.1;37.4.1. Cell Sheet for Periodontal Regeneration;509
14.4.4.2;37.4.2. Cell Pellet for Periodontal Regeneration;510
14.4.5;37.5. Gene Therapy for Periodontal Tissue Engineering;510
14.4.5.1;37.5.1. The Biology of Gene Therapy;511
14.4.5.2;37.5.2. Gene Therapy for Periodontal Regeneration;511
14.4.6;37.6. Conclusion;512
14.4.7;Acknowledgments;512
14.4.8;Acronyms and Abbreviations;512
14.4.9;References;513
15;Part VIII: Craniofacial Tissue Engineering;516
15.1;Chapter 38: Molecular Strategies in the Study and Repair of Palatal Defects;518
15.1.1;38.1. Introduction;518
15.1.2;38.2. Genetic and Environmental Influences;519
15.1.2.1;38.2.1. Linkage Studies;519
15.1.2.2;38.2.2. Association Studies;519
15.1.2.3;38.2.3. Genome-Wide Association Studies;519
15.1.3;38.3. Signal Transduction and Orofacial Development;520
15.1.3.1;38.3.1. Transforming Growth Factor ß;520
15.1.3.2;38.3.2. Sonic Hedgehog;521
15.1.3.3;38.3.3. Wnt Proteins;521
15.1.4;38.4. Tissue Engineering Strategies for the Repair of Palatal and Other Craniofacial Defects;522
15.1.4.1;38.4.1. Stem Cells;524
15.1.4.2;38.4.2. Scaffolds;524
15.1.4.3;38.4.3. Culture Systems;525
15.1.4.4;38.4.4. Enhancing Vascularization of Bioengineered Constructs;525
15.1.4.5;38.4.5. Manipulation of Gene Expression;526
15.1.4.6;38.4.6. Clinical Reports;526
15.1.5;38.5. Summary;527
15.1.6;Acknowledgments;527
15.1.7;Abbreviations;527
15.1.8;References;527
15.2;Chapter 39: Molecular Genetics and Biology of Craniofacial Craniosynostoses;532
15.2.1;39.1. Craniofacial Synostosis Overview;532
15.2.1.1;39.1.1. Normal Calvarial and Facial Anatomy, Histology, Definition of Synostosis;532
15.2.1.2;39.1.2. Normal Timing of Fusion of Craniofacial Sutures;533
15.2.1.3;39.1.3. Craniosynostosis;533
15.2.2;39.2. Molecular Genetics of Craniosynostosis;534
15.2.2.1;39.2.1. Syndromic Craniosynostosis;534
15.2.2.1.1;39.2.1.1. FGFRs;534
15.2.2.1.2;39.2.1.2. TWIST1 and RUNX2;536
15.2.2.1.3;39.2.1.3. EFNB1;536
15.2.2.1.4;39.2.1.4. TGFBR;536
15.2.2.1.5;39.2.1.5. Other Genes;536
15.2.2.2;39.2.2. Single Suture Synostosis;538
15.2.2.3;39.2.3. Transcriptomic Clues to the Cause of Single Suture Craniosynostosis;539
15.2.3;39.3. Impact of Craniosynostosis Mutations on Protein Structure and Function;539
15.2.3.1;39.3.1. Structural Analysis of Unique Craniosynostosis Variants;539
15.2.3.2;39.3.2. Understanding Domain Function through Dysfunction;541
15.2.4;39.4. Integration of Molecular Genetics and Suture Biology;544
15.2.4.1;39.4.1. The Regulation of Calvarial and Facial Suture Patency;544
15.2.4.2;39.4.2. Fgf Signaling Controls Osteoblast Proliferation in Craniofacial Sutures;546
15.2.4.3;39.4.3. Crosstalk with Other Signaling Pathways: the TGFbeta and BMP Pathways;547
15.2.4.4;39.4.4. Eph/ephrins: Roles in Osteoblast Communication and Boundary Formation;547
15.2.4.5;39.4.5. A Possible Role for Cilia in Suture Biology;547
15.2.4.6;39.4.6. Other Molecular Players;548
15.2.5;39.5. Targets for Stem Cell Therapies and Tissue Engineering Strategies in Craniofacial Disorders;548
15.2.6;References;549
15.3;Chapter 40: Tissue Engineering Craniofacial Bone Products;554
15.3.1;40.1. Introduction: The Need for Tissue-Engineered Bone Products;554
15.3.1.1;40.1.1. Key Concepts;555
15.3.2;40.2. Strategies for Tissue Engineering of Bone Substitutes;555
15.3.2.1;40.2.1. In Vivo Tissue Engineering;556
15.3.2.2;40.2.2. Ex Vivo Tissue Engineering;556
15.3.3;40.3. Components of Te Bone Products;556
15.3.3.1;40.3.1. Human Osteogenic Cells;556
15.3.3.1.1;40.3.1.1. Primary Osteoblasts from the Bone Tissue;557
15.3.3.1.2;40.3.1.2. Periosteum-Derived Mesenchymal Progenitors;557
15.3.3.1.3;40.3.1.3. Bone Marrow-Derived Stromal/Stem Cell Populations;557
15.3.3.1.4;40.3.1.4. Adipose Tissue-Derived Stromal/Stem Cell Populations;557
15.3.3.2;40.3.2. Biomaterial Scaffolds;557
15.3.3.3;40.3.3. Osteoinductive Signals;558
15.3.3.4;40.3.4. Technologies for Cell Processing and In Vitro Cultivation of Bone Substitutes;558
15.3.4;40.4. The Properties and Clinical Use of Te Bone Products;559
15.3.4.1;40.4.1. TE Bone Products Containing Osteoconductive Scaffolds with Osteoinductive Factors;562
15.3.4.2;40.4.2. Custom-Made TE Bone Substitutes Containing Viable Cells for the Treatment of Individual Patients;563
15.3.4.2.1;40.4.2.1. Periosteal Progenitor-Derived Bone Substitutes;563
15.3.4.2.2;40.4.2.2. Primary Osteoblast-Derived Bone Substitutes;564
15.3.4.2.3;40.4.2.3. Bone Marrow Stromal/Stem Cell-Derived Bone Substitutes;564
15.3.4.2.4;40.4.2.4. Adipose Tissue Stromal/Stem Cell-Derived Bone Substitutes;566
15.3.4.3;40.4.3. Commercial TE Bone Products Containing Viable Cells;566
15.3.4.3.1;40.4.3.1. Biotissue Technologies Periosteum-Derived Tissue-Engineered Bone (BioSeed-Oral Bone);566
15.3.4.3.2;40.4.3.2. Osiris Therapeutics/NuVasive Adult Stem C ells on Allogeneic Bone Matrix (Osteocel);567
15.3.4.3.3;40.4.3.3. Aastrom Biosciences Bone Marrow-Derived Cell Transplants (Tissue Repair Cells);567
15.3.4.3.4;40.4.3.4. Mesoblast Mesenchymal Precursor Cells (NeoFuse);568
15.3.5;40.5. Future Challenges in the Development and Application of Te Bone Products;568
15.3.6;40.6. Conclusion;568
15.3.7;Acronyms and Abbreviations;569
15.3.8;References;569
15.4;Chapter 41: Craniofacial Cartilage Tissue Engineering;574
15.4.1;41.1. Introduction;574
15.4.1.1;41.1.1. Key Concepts;575
15.4.2;41.2. Cartilage as a Tissue Source;575
15.4.3;41.3. Cell Expansion in Monolayer Culture;576
15.4.4;41.4. Three-Dimensional Culture Systems;577
15.4.5;41.5. Optimizing the Growth Environment;578
15.4.5.1;41.5.1. Growth Factor Stimulation;578
15.4.5.2;41.5.2. Cartilage Tissue Engineering with Human Serum;578
15.4.5.3;41.5.3. Dynamic Culture Systems;578
15.4.6;41.6. Stem Cells: An Alternative Cell Source;580
15.4.7;41.7. In Vivo Maturation of Tissue-Engineered Cartilage;581
15.4.8;41.8. Future Challenges;582
15.4.9;41.9. Conclusion;582
15.4.10;Abbreviations;582
15.4.11;References;582
15.5;Chapter 42: Tendon and Ligament Tissue Engineering;586
15.5.1;42.1. Introduction and current treatment;586
15.5.1.1;42.1.1. Ligament/Tendon in the Craniofacial Region;586
15.5.1.2;42.1.2. Anterior Cruciate Ligament and Posterior Cruciate Ligament;587
15.5.1.3;42.1.3. Supraspinatus Tendon;588
15.5.2;42.2. Tissue Engineering strategies;589
15.5.2.1;42.2.1. Cells;589
15.5.2.2;42.2.2. Soluble Factors;590
15.5.2.3;42.2.3. Scaffolds;590
15.5.2.3.1;42.2.3.1. Collagen;591
15.5.2.3.2;42.2.3.2. Hyaluronic Acid, Chitosan, and Alginate;591
15.5.2.3.3;42.2.3.3. Silk;591
15.5.2.3.4;42.2.3.4. Synthetic Materials;592
15.5.3;42.3. Mechanical signals;592
15.5.4;42.4. Gene transfer for ligament/tendon regeneration;593
15.5.5;42.5. Animal studies;593
15.5.6;42.6. Human trials;595
15.5.7;42.7. Conclusions;595
15.5.8;Abbreviations;595
15.5.9;References;596
15.6;Chapter 43: Soft Tissue Reconstruction: Skeletal Muscle Engineering ;600
15.6.1;43.1. Introduction;600
15.6.2;43.2. Skeletal muscle;601
15.6.2.1;43.2.1. Gross Structure;601
15.6.2.2;43.2.2. Ultrastructure;602
15.6.2.3;43.2.3. Extracellular Matrix;602
15.6.2.4;43.2.4. Integration with Other Systems;602
15.6.2.5;43.2.5. Satellite Cells;603
15.6.3;43.3. Introduction to craniofacial growth, as well as common congenital and acquired craniofacial muscle abnormalities and ...;604
15.6.3.1;43.3.1. Craniofacial Growth;604
15.6.3.2;43.3.2. Congenital and Acquired Craniofacial Abnormalities and Injuries;605
15.6.3.2.1;43.3.2.1. Muscle Hypoplasia;605
15.6.3.2.2;43.3.2.2. The Importance of Muscle Function to the Temporomandibular Joint;605
15.6.3.2.3;43.3.2.3. Muscle Trauma;605
15.6.3.3;43.3.3. Current Craniofacial Reconstructive Techniques;606
15.6.3.4;43.3.4. The Promise of Regenerative Medicine (RM) and Tissue Engineering (TE) for Craniofacial Reconstruction;606
15.6.4;43.4. Engineering skeletal muscle;607
15.6.4.1;43.4.1. Isolation of Muscle Precursor Cells;607
15.6.4.2;43.4.2. Synthetic Scaffold;608
15.6.4.3;43.4.3. Biomimetic Scaffolds;609
15.6.4.3.1;43.4.3.1. Collagen Matrices;609
15.6.4.3.2;43.4.3.2. Fibrin Matrices;609
15.6.4.3.3;43.4.3.3. Composite Matrices;610
15.6.5;43.5. Advancing maturation and function of engineered skeletal muscle;610
15.6.5.1;43.5.1. Mechanical and Electrical Signals;610
15.6.5.2;43.5.2. Addition and Integration of Other Cell Types;611
15.6.5.2.1;43.5.2.1. Growth Factors and Extracellular Matrix Proteins;612
15.6.5.2.2;43.5.2.2. Hypoxia;613
15.6.6;43.6. Novel technologies for in vivo muscle regeneration, repair, and replacement;613
15.6.6.1;43.6.1. Technologies for VML Repair Using Scaffold-Only Approaches;613
15.6.6.2;43.6.2. Technologies for VML Repair Using Scaffold Plus Cells;613
15.6.6.3;43.6.3. Summary and Conclusions;619
15.6.7;43.7. Future clinical implications;619
15.6.7.1;43.7.1. The Technology Gap;619
15.6.7.2;43.7.2. Application to the Craniofacial Region;619
15.6.7.2.1;43.7.2.1. Potential First Clinical Application;619
15.6.8;43.8. Conclusions;620
15.6.9;Abbreviations;620
15.6.10;References;620
15.7;Chapter 44: Multi-Tissue Interface Bioengineering;626
15.7.1;44.1. Introduction;626
15.7.2;44.2. Monolithic Scaffold-Based Approaches;627
15.7.3;44.3. Scaffolds with Discrete Functional Regions;628
15.7.4;44.4. Tissue Engineering Technologies to Improve Current Surgical Techniques;631
15.7.5;44.5. Future Directions;631
15.7.6;44.6. Conclusion;632
15.7.7;References;632
15.8;Chapter 45: Soft Tissue Reconstruction: Adipose Tissue Engineering;636
15.8.1;45.1. Introduction;636
15.8.2;45.2. Anatomy and Function of Adipose Tissue;636
15.8.2.1;45.2.1. Composition and Anatomy;636
15.8.2.2;45.2.2. Physiologic Functions;637
15.8.2.3;45.2.3. Diseases of Craniofacial Soft Tissue: Parry-Romberg Syndrome;637
15.8.3;45.3. Current Approach to Soft Tissue Reconstruction in The Craniofacial Region;637
15.8.3.1;45.3.1. Synthetic Fillers;637
15.8.3.2;45.3.2. Autologous Tissue Transfer;637
15.8.3.3;45.3.3. Fat Grafting;637
15.8.4;45.4. Adipose Tissue Engineering: Biomaterials, Stem Cells, and the Era of Regenerative Medicine;638
15.8.4.1;45.4.1. Biomaterials;638
15.8.4.1.1;45.4.1.1. Synthetic Polymers;638
15.8.4.1.2;45.4.1.2. Natural Polymers;639
15.8.4.2;45.4.2. Cell Sources;639
15.8.4.2.1;45.4.2.1. Human Mesenchymal Stem Cells;639
15.8.4.2.2;45.4.2.2. Pluripotent Cells;639
15.8.4.3;45.4.3. Culture Methodology;640
15.8.5;45.5. Current Research;640
15.8.6;45.6. Ethics;640
15.8.7;45.7. Conclusion;640
15.8.8;References;640
16;Part IX: Bioengineering Organs in Head and Neck;644
16.1;Chapter 46: Salivary Gland Tissue Engineering and Repair;646
16.1.1;46.1. Introduction;646
16.1.2;46.2. Salivary Gland Structure and Function;646
16.1.2.1;46.2.1. Salivary Gland Physiology and Fluid Secretion;647
16.1.2.2;46.2.2. Protein Secretion;647
16.1.3;46.3. Salivary Gland Atrophy and Repair;647
16.1.3.1;46.3.1. Rationale for Tissue Replacement;648
16.1.3.2;46.3.2. Salivary Gland Repair;648
16.1.3.3;46.3.3. Innervation and Vascularization;650
16.1.4;46.4. Biomaterial Scaffolds;650
16.1.4.1;46.4.1. Synthetic and Biologically Derived Hydrogel Scaffolds;650
16.1.4.2;46.4.2. Hyaluronic Acid-Based Hydrogels;651
16.1.4.3;46.4.3. Hyaluronic Acid-Based Hydrogel Particles;651
16.1.5;46.5. Recent Advances in Salivary Gland Tissue Engineering;652
16.1.5.1;46.5.1. Differentiation of Salivary Gland Cells;652
16.1.5.2;46.5.2. Branching Morphogenesis;652
16.1.6;46.6. Conclusion and Future Work;653
16.1.7;Acknowledgment;654
16.1.8;Abbreviations;654
16.1.9;References;654
16.2;Chapter 47: Tissue Engineering of Larynx;658
16.2.1;47.1. Introduction;658
16.2.1.1;47.1.1. Key Concepts;659
16.2.2;47.2. Laryngeal Anatomy;659
16.2.2.1;47.2.1. General Structure;659
16.2.2.2;47.2.2. Vocal Fold Structure and Function;659
16.2.2.2.1;47.2.2.1. Layers of the Vocal Fold Lamina Propria;660
16.2.2.3;47.2.3. Lamina Propria Extracellular Matrix;661
16.2.2.3.1;47.2.3.1. Fibrous Proteins;662
16.2.2.3.2;47.2.3.2. Interstitial Elements;663
16.2.3;47.3. Vocal Fold Microstructure Restoration;664
16.2.3.1;47.3.1. Scaffolds;664
16.2.3.1.1;47.3.1.1. Hyaluronic Acid Derivatives;665
16.2.3.1.2;47.3.1.2. Hydrogels;665
16.2.3.1.3;47.3.1.3. Microgels;665
16.2.3.1.4;47.3.1.4. 2,3-Dialdehydecellulose Membranes;665
16.2.3.1.5;47.3.1.5. Decellularized Xenogeneic ECM;666
16.2.3.1.6;47.3.1.6. Synthetic Elastomers;666
16.2.3.2;47.3.2. Cell Transplantation;666
16.2.3.2.1;47.3.2.1. Fibroblasts;666
16.2.3.2.2;47.3.2.2. Stem Cells;667
16.2.3.2.2.1;47.3.2.2.1. Human Embryonic Stem Cells;667
16.2.3.2.2.2;47.3.2.2.2. Bone Marrow-Derived Mesenchymal Stem Cells;667
16.2.3.2.2.3;47.3.2.2.3. Adipose-Derived Mesenchymal Stem Cells;667
16.2.3.3;47.3.3. Bioactive Factors;667
16.2.3.3.1;47.3.3.1. Basic Fibroblast Growth Factor;667
16.2.3.3.2;47.3.3.2. Hepatocyte Growth Factor;667
16.2.3.4;47.3.4. Mechanotransduction;668
16.2.4;47.4. Larynx Superstructure Bioengineering;668
16.2.4.1;47.4.1. Cartilage Regeneration;668
16.2.4.1.1;47.4.1.1. Tissue-Engineered Cartilage;668
16.2.4.1.2;47.4.1.2. Polypropylene Mesh Grafts;668
16.2.4.2;47.4.2. Decellularized Human Larynx;669
16.2.5;47.5. Neuromuscular Regeneration;669
16.2.5.1;47.5.1. Neurotrophic Factors;670
16.2.5.2;47.5.2. Artificial Nerve Conduits;670
16.2.5.3;47.5.3. Muscle Regeneration;670
16.2.6;47.6. Conclusion;671
16.2.7;Abbreviations;671
16.2.8;References;671
16.3;Chapter 48: The Bio-Artificial Trachea;674
16.3.1;48.1. Introduction;674
16.3.1.1;48.1.1. Tracheal Pathology: The Clinical Need;675
16.3.1.2;48.1.2. Tissue-Engineered Trachea: The Concept;675
16.3.2;48.2. In Vitro Scaffold Assessment for Trachea Tissue Engineering;676
16.3.3;48.3. In Vivo Scaffold Assessment for Trachea Tissue Engineering;678
16.3.4;48.4. Tissue Engineering The Trachea;680
16.3.5;48.5. Conclusion;682
16.3.6;Acronyms and Abbreviations;683
16.3.7;References;683
16.4;Chapter 49: Tissue Engineering of the Esophagus;686
16.4.1;49.1. Introduction;686
16.4.2;49.2. Anatomy, Histology, and Physiology;686
16.4.2.1;49.2.1. Histology;686
16.4.2.2;49.2.2. Physiology;687
16.4.2.3;49.2.3. Potential Clinical Indications;687
16.4.2.3.1;49.2.3.1. Barrett’s Esophagus (BE);687
16.4.2.3.2;49.2.3.2. Esophageal Cancer;687
16.4.2.3.3;49.2.3.3. Esophageal Atresia (EA);687
16.4.2.3.4;49.2.3.4. Trauma;688
16.4.2.3.5;49.2.3.5. Alkali and Acid Ingestion;688
16.4.2.4;49.2.4. Surgical Therapy;688
16.4.3;49.3. Tissue Engineering;688
16.4.3.1;49.3.1. Cell Sources;689
16.4.3.2;49.3.2. Scaffolds;690
16.4.3.2.1;49.3.2.1. Esophagus Extracellular Matrix Scaffolds;690
16.4.3.2.2;49.3.2.2. Extracellular Matrix Derived from Other Organs;691
16.4.3.3;49.3.3. Artificial Scaffolds;693
16.4.3.4;49.3.4. Clinical Trials;695
16.4.4;49.4. Conclusion;695
16.4.5;Acronyms and Abbreviations;696
16.4.6;References;696
17;Part X: Tissue Engineering Skin and Oral Mucosa;700
17.1;Chapter 50: Cell and Molecular Biology of Wound Healing;702
17.1.1;50.1. Introduction;702
17.1.2;50.2. Evolutionary Perspective to Mucosal and Skin Wound Healing;703
17.1.3;50.3. Inflammation and Wound Healing;704
17.1.3.1;50.3.1. Platelets Initiate Wound Healing;704
17.1.3.2;50.3.2. Neutrophils Dictate the Onset and Resolution of Inflammation in Wounds;704
17.1.3.3;50.3.3. Macrophages: Important Modulators of Wound Healing;706
17.1.4;50.4. Re-Epithelialization of Wounds;708
17.1.4.1;50.4.1. The Process of Re-Epithelialization;708
17.1.4.2;50.4.2. Activation and Mobilization of Wound Edge Keratinocytes;708
17.1.4.3;50.4.3. Active Re-Epithelialization;709
17.1.4.4;50.4.4. Final Stages of Re-Epithelialization;711
17.1.5;50.5. Connective Tissue Wound Healing: Granulation Tissue Formation and Remodeling;711
17.1.5.1;50.5.1. General Overview;711
17.1.5.2;50.5.2. Origin of Connective Tissue Cells that Heal the Wounds;711
17.1.5.3;50.5.3. Cell Activation: Initial Step in Connective Tissue Wound Healing;713
17.1.5.4;50.5.4. Cell Migration into the Wound Provisional Matrix;713
17.1.5.5;50.5.5. Myofibroblasts Produce the Granulation Tissue Matrix and Remodel it;713
17.1.5.6;50.5.6. Angiogenesis;715
17.1.5.7;50.5.7. Remodeling Stage of Wound Healing;717
17.1.5.8;50.5.8. Excessive Scar Formation and Fibrosis;718
17.1.6;50.6. Conclusions;719
17.1.7;Acknowledgments;720
17.1.8;Abbreviations;720
17.1.9;References;720
17.2;Chapter 51: Models of Differential Wound Healing;724
17.2.1;51.1. Introduction;724
17.2.2;51.2. Cutaneous Wound Healing (Adult Vs. Fetal);726
17.2.2.1;51.2.1. Inflammatory Response;726
17.2.2.1.1;51.2.1.1. Inflammatory Cells;726
17.2.2.1.2;51.2.1.2. Inflammatory Cytokines;726
17.2.2.2;51.2.2. Extracellular Matrix (ECM);727
17.2.2.2.1;51.2.2.1. Fibroblasts;727
17.2.2.2.2;51.2.2.2. Collagen;727
17.2.2.2.3;51.2.2.3. Other ECM Proteins and Modulators;728
17.2.3;51.3. Oral Mucosa;729
17.2.3.1;51.3.1. Inflammatory Response;729
17.2.3.1.1;51.3.1.1. Inflammatory Cells;729
17.2.3.1.2;51.3.1.2. Inflammatory Cytokines;729
17.2.3.2;51.3.2. Saliva;730
17.2.3.3;51.3.3. Extracellular Matrix;730
17.2.3.3.1;51.3.3.1. Fibroblast;730
17.2.3.3.2;51.3.3.2. Collagen and Other ECM Molecules;731
17.2.4;51.4. Summary;732
17.2.5;References;732
17.3;Chapter 52: Bioengineering Skin Constructs;736
17.3.1;52.1. Introduction;736
17.3.2;52.2. Traditional Treatments for Skin Injuries;737
17.3.2.1;52.2.1. Autograft;737
17.3.2.2;52.2.2. Allograft;737
17.3.2.3;52.2.3. Wound Dressing;738
17.3.3;52.3. Tissue Engineering Approach for Skin Repair;738
17.3.3.1;52.3.1. The Need for Tissue-Engineered Skin Substitutes;738
17.3.3.2;52.3.2. The Key Factors of Tissue-Engineered Skin;738
17.3.3.2.1;52.3.2.1. Scaffolds;738
17.3.3.2.2;52.3.2.2. Cells;740
17.3.3.2.3;52.3.2.3. Bioactive Factors;741
17.3.4;52.4. Current Progress;742
17.3.4.1;52.4.1. Tissue-Engineered Epidermis;742
17.3.4.2;52.4.2. Tissue-Engineered Dermis;742
17.3.4.3;52.4.3. Tissue-Engineered Skin;744
17.3.5;52.5. Important Challenges and Strategies;745
17.3.5.1;52.5.1. Angiogenesis;745
17.3.5.2;52.5.2. Scarring;746
17.3.5.3;52.5.3. Appendages;747
17.3.6;52.6. Conclusions and Future Perspectives;749
17.3.7;References;749
17.4;Chapter 53: Three-Dimensional Reconstruction of Oral Mucosa: Tissue Engineering Strategies;754
17.4.1;53.1. Introduction;754
17.4.2;53.2. Conventional treatment for reconstruction of oral mucosa defects;754
17.4.3;53.3. Goals of oral mucosa Tissue Engineering;755
17.4.4;53.4. Strategies for Tissue Engineering of oral mucosa;755
17.4.4.1;53.4.1. Epithelial Sheets;755
17.4.4.2;53.4.2. Dermal Substitutes;756
17.4.4.3;53.4.3. Bi-Layered;756
17.4.5;53.5. Pre-clinical and clinical studies on teoms for intraoral and extraoral applications;757
17.4.5.1;53.5.1. In Vivo Animal Studies;757
17.4.5.2;53.5.2. Human Clinical Application (Intraoral Grafting);757
17.4.5.3;53.5.3. Pre-Clinical and Clinical Applications (Extraoral Grafting);757
17.4.6;53.6. Regulatory issues of tissue-engineered product manufacturing;759
17.4.7;53.7. Challenges;759
17.4.8;53.8. Future strategies;759
17.4.9;53.9. Conclusions;760
17.4.10;References;761
18;Part XI: Tissue Engineered Implant Dentistry;766
18.1;Chapter 54: Dental Implantology and Implants: Basic Aspects and Tissue Interface ;768
18.1.1;54.1. Introduction;768
18.1.2;54.2. History and readers;768
18.1.3;54.3. Anatomy of dental implants and clinical aspects;769
18.1.4;54.4. “Stem cells” and Tissue Engineering in implant dentistry;770
18.1.5;54.5. Tooth versus dental implant;770
18.1.6;54.6. Biological principles of hard and soft tissue integration;772
18.1.7;54.7. Surface modifications of titanium implants;773
18.1.8;54.8. Implant failures;774
18.1.9;54.9. Alternative materials;775
18.1.10;54.10. Future aspects;775
18.1.11;References;776
18.2;Chapter 55: Dental Implant-Guided Bone Tissue Engineering;782
18.2.1;55.1. Introduction: Key Concepts;782
18.2.2;55.2. Dental Implants;783
18.2.3;55.3. Alveolar Ridge Bone Loss: the Clinical Problem;784
18.2.4;55.4. Current Approaches for Alveolar Ridge Augmentation;784
18.2.4.1;55.4.1. Onlay Block Grafts;784
18.2.4.2;55.4.2. Guided Bone Regeneration (GBR);784
18.2.4.3;55.4.3. Distraction Osteogenesis (DO);784
18.2.5;55.5. The Concept of Implant-Guided Alveolar Ridge Bone Tissue Engineering;785
18.2.6;55.6. Animal Models and Pre-Clinical Testing Results for Implant-Guided Bone Tissue Engineering;785
18.2.6.1;55.6.1. The Development of a Murine Calvarial Dental Implant Model;786
18.2.6.2;55.6.2. The Development of a Rat Extraoral Mandible Model;786
18.2.6.3;55.6.3. The Development of a Rabbit Extraoral Mandible Model;788
18.2.6.4;55.6.4. Dog Intraoral Model;789
18.2.6.5;55.6.5. Minipig Intraoral Model;789
18.2.7;55.7. Bioactive Osteogenic Molecules for Use in Alveolar Ridge Augmentation;789
18.2.8;55.8. Delivery of Osteogenic Molecules from Dental Implants and Scaffolds;791
18.2.8.1;55.8.1. Titanium Implants for Delivery of Osteogenic Agents;791
18.2.8.2;55.8.2. Calcium Phosphate Biomaterials;791
18.2.8.3;55.8.3. Hydroxyapatite Coated Collagen Scaffold;792
18.2.8.4;55.8.4. Polyethylene Glycol Hydrogel Scaffold;792
18.2.8.5;55.8.5. Demineralized Bone Matrix;792
18.2.9;55.9. Cell-Based Alveolar Ridge Augmentation Approaches;792
18.2.10;55.10. Conclusions;793
18.2.11;References;794
18.3;Chapter 56: Periodontal Tissue Engineering Around Dental Implants;798
18.3.1;56.1. Introduction;798
18.3.2;56.2. PDL Development;798
18.3.2.1;56.2.1. Embryogenesis of PDL Attachment;798
18.3.2.2;56.2.2. Osseointegration Versus PDL Integration;799
18.3.3;56.3. Tissue Engineering PDL Tissues;799
18.3.3.1;56.3.1. Growth Factors;800
18.3.3.2;56.3.2. Stem Cells in PDL Tissue Engineering;800
18.3.3.3;56.3.3. Scaffolds in PDL Tissue Engineering;801
18.3.3.4;56.3.4. Titanium Surface and PDL Regeneration;801
18.3.4;56.4. Review of Literature;802
18.3.5;56.5. Conclusion;805
18.3.6;References;805
19;Part XII: Tissue Engineering in Orthodontics & Dentofacial Orthopedics;808
19.1;Chapter 57: Biological and Molecular Mediators During Orthodontic Tooth Movement;810
19.1.1;57.1. Introduction;810
19.1.1.1;57.1.1. Key Concepts;810
19.1.2;57.2. Molecular Activities During OTM;811
19.1.2.1;57.2.1. Early Phases of OTM;811
19.1.2.1.1;57.2.1.1. Extracellular Matrix;812
19.1.2.1.2;57.2.1.2. Osteocytes;812
19.1.2.1.3;57.2.1.3. Periodontal Fibroblasts;813
19.1.2.1.4;57.2.1.4. Inflammation;813
19.1.2.2;57.2.2. Later Phases of OTM;814
19.1.2.2.1;57.2.2.1. Bone Resorption (Osteoclasts);814
19.1.2.2.2;57.2.2.2. Bone Formation (Osteoblasts);815
19.1.2.3;57.2.3. Role of Prostaglandins during OTM;815
19.1.3;57.3. Challenges and Future Directions;816
19.1.4;57.4. Conclusion;817
19.1.5;Acknowledgment;817
19.1.6;References;817
19.2;Chapter 58: Accelerated Tooth Movement;820
19.2.1;58.1. Introduction;820
19.2.2;58.2. Orthodontic Tooth Movement (OTM) and Inflammatory Markers;821
19.2.3;58.3. Inflammatory Markers as a Method of Increasing the Rate of Tooth Movement;823
19.2.4;58.4. Physical Stimulation as a Method of Increasing the Rate of Tooth Movement;826
19.2.4.1;58.4.1. Mechanical Stimulation to Increase the Rate of Tooth Movement;826
19.2.4.2;58.4.2. Heat, Light, Electric Currents, and Laser to Increase the Rate of Tooth Movement;827
19.2.5;58.5. Chemical Agents to Increase the Rate of Tooth Movement;827
19.2.6;58.6. Summary and Future Directions;828
19.2.7;Abbreviations;828
19.2.8;References;828
19.3;Chapter 59: Stem Cell Therapy for Orthodontists: A Conceptual Introduction ;832
19.3.1;59.1. Introduction;832
19.3.1.1;59.1.1. New Ideas and the Nature of Social Change;833
19.3.1.2;59.1.2. “NewThink” for a New Century;833
19.3.2;59.2. Tissue Engineering: A Relevant Science in Orthodontics;833
19.3.2.1;59.2.1. Orthodontic Tissue Engineering (OTE);834
19.3.2.2;59.2.2. Bone Stem Cell Grafting Principles;834
19.3.3;59.3. Tissue Engineering: Recent Clinical Background;835
19.3.4;59.4. To Extract or not to Extract;836
19.3.4.1;59.4.1. Stem Cell Basics;838
19.3.4.2;59.4.2. Classification of Mesenchymal Stem Cells;839
19.3.5;59.5. Cluster Identification, Pharmaco-orthodontics, and Genetic Manipulation;840
19.3.5.1;59.5.1. Tissue Engineering Constructs and Scaffolds;840
19.3.5.2;59.5.2. Clinical Characteristics and Sources of Stem Cells;841
19.3.5.3;59.5.3. Extra Oral Sources of Stem Cells;841
19.3.5.4;59.5.4. Clinical Applications of Stem Cells and Bone Progenitor Cells;842
19.3.5.4.1;59.5.4.1. Autogenous Stem Cell Targeting;842
19.3.5.4.2;59.5.4.2. Allografts: Same Species, Different Individuals;843
19.3.5.4.3;59.5.4.3. Culture-Expanded Autogenous Grafts;843
19.3.5.4.4;59.5.4.4. Genetically Modified Stem Cell Grafts;843
19.3.5.4.5;59.5.4.5. Ex Vivo Tissue Generation and Transplantation;843
19.3.6;59.6. Challenges/Considerations in ORTHODONTIC Tissue Engineering;844
19.3.6.1;59.6.1. The Infection Challenge;844
19.3.6.2;59.6.2. Mass Transport and Diffusion Distance;845
19.3.7;59.7. Mechanobiology and the Peri-Orthodontic Hypothesis: Ote as Applied Molecular Biology;845
19.3.8;59.8. Beyond the Ligament: A New Perspective on Bone Behavior;847
19.3.8.1;59.8.1. Molecular Mechanisms;847
19.3.8.2;59.8.2. Bending Bone Bends DNA;848
19.3.9;59.9. Future Strategies;849
19.3.10;59.10. Epilogue as Prologue;850
19.3.11;Dedication;851
19.3.12;Acknowledgments;851
19.3.13;References;851
19.4;Chapter 60: Ultrasound Applications in Orthodontics;856
19.4.1;60.1. Introduction;856
19.4.2;60.2. Orthodontics and Stem Cells;857
19.4.3;60.3. Applications of Ultrasound in Medicine and Biology;858
19.4.3.1;60.3.1. Therapeutic Low-Intensity Pulsed Ultrasound (LIPUS);858
19.4.3.2;60.3.2. Future Applications of Lipus in Orthodontics;859
19.4.4;60.4. Conclusions;859
19.4.5;References;860
20;Part XIII: Transplantation of Engineered Tissue Constructs;862
20.1;Chapter 61: Immunotherapy in Transplantation;864
20.1.1;61.1. Introduction;864
20.1.2;61.2. Immunomodulation Properties of Mesenchymal Stem Cells;864
20.1.2.1;61.2.1. Mesenchymal Stem Cells and Immune Cells;864
20.1.2.1.1;61.2.1.1. Interaction with T-Lymphocytes;865
20.1.2.1.2;61.2.1.2. Interaction with B-Lymphocytes;865
20.1.2.1.3;61.2.1.3. Interaction with Natural killer (NK) Cells;865
20.1.2.1.4;61.2.1.4. Interaction with Dendritic Cells (DCs);865
20.1.2.1.5;61.2.1.5. Interaction with Regulatory T-Cells (Tregs) and T-Helper 17 Cells (Th17);866
20.1.2.2;61.2.2. Pre-Clinical and Clinical Application of Mesenchymal Stem Cell Transplantation;866
20.1.3;61.3. Immunomodulation Properties of Mesenchymal Stem Cells in Dentistry;867
20.1.3.1;61.3.1. Mesenchymal Stem Cell from Jaw Bone Marrow;867
20.1.3.2;61.3.2. Dental Pulp Stem Cells;868
20.1.3.3;61.3.3. Periodontal Ligament Stem Cells;868
20.1.3.4;61.3.4. Stem Cells from Apical Papilla;868
20.1.3.5;61.3.5. Gingival Mesenchymal Stem Cells;868
20.1.4;61.4. Conclusion and Future Aspects;869
20.1.5;References;870
20.2;Chapter 62: Non-Invasive In Vivo Imaging of Transplanted Cells and Biomaterials;874
20.2.1;62.1. Introduction;874
20.2.1.1;62.1.1. Key Concepts;875
20.2.2;62.2. Diagnostic Imaging in Dentistry;875
20.2.3;62.3. The Challenge of Non-Invasive Imaging in Regenerative Dentistry;877
20.2.4;62.4. Approaches to Non-Invasively Visualize Implanted Cells;877
20.2.5;62.5. Visualizing Cells in the Context of Tissue Engineering/Regenerative Medicine;879
20.2.6;62.6. Conclusion;881
20.2.7;Acronyms and Abbreviations;881
20.2.8;References;881
21;Part XIV: Research Ethics and Law;886
21.1;Chapter 63: Ethics and Emerging Laws in Stem Cell Science;888
21.1.1;63.1. Introduction;888
21.1.2;63.2. Early Responses from Philosophical Ethics;888
21.1.2.1;63.2.1. Some Religious Viewpoints;889
21.1.2.2;63.2.2. Some Situated Ethical Viewpoints;890
21.1.3;63.3. Some Early Regulatory Responses to Human Embryonic Stem Cells;890
21.1.3.1;63.3.1. United States of America: Early Response;890
21.1.3.2;63.3.2. United Kingdom;891
21.1.3.3;63.3.3. Spain;891
21.1.3.4;63.3.4. Japan;892
21.1.3.5;63.3.5. India;892
21.1.3.6;63.3.6. Elsewhere;892
21.1.4;63.4. The Emergence of Somatic Cell Nuclear Transfer and the Demand for Ova;892
21.1.5;63.5. Forgotten Fetuses;893
21.1.6;63.6. Interspecies Embryos;893
21.1.7;63.7. The Fall of Professor Hwang Woo-Suk;894
21.1.8;63.8. The Arrival of Induced Pluripotency Stem Cells;894
21.1.9;63.9. Ongoing Issues;894
21.1.10;63.10. Conclusion;895
21.1.11;Acknowledgments;896
21.1.12;Acronyms and Abbreviations;896
21.1.13;References;896
21.2;Chapter 64: Ethical Aspects of Tissue Engineered Products;898
21.2.1;64.1. Introduction;898
21.2.2;64.2. Ethical Challenges in Cell Based Therapies;898
21.2.2.1;64.2.1. Fetal Cells;898
21.2.2.2;64.2.2. Private Banking of Cells;899
21.2.3;64.3. Safety;899
21.2.4;64.4. Informed Consent;900
21.2.5;64.5. Clinical Trials of TE Products;901
21.2.6;64.6. Intellectual Property Protection;901
21.2.6.1;64.6.1. International Laws;901
21.2.7;64.7. Discussion;902
21.2.8;Abbreviation;902
21.2.9;References;903
21.3;Chapter 65: Problems and Pitfalls in Tissue-Engineered Therapy;904
21.3.1;65.1. Introduction;904
21.3.2;65.2. “Classic” Development Pathway;904
21.3.3;65.3. Real World Examples;905
21.3.3.1;65.3.1. Apligraf;905
21.3.3.2;65.3.2. Dermagraft;905
21.3.3.3;65.3.3. INTEGRA® Dermal Regeneration Template (IDRT);906
21.3.3.4;65.3.4. Epicel;907
21.3.4;65.4. Lessons and Conclusion;907
21.3.5;Acknowledgment;908
22;Glossary;910
23;Nomenclature;916
24;Index;922

Leseproben

List of Contributors
Samad Ahadian, PhD     WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, Japan Kentaro Akiyaman, DDS, PhD     Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Kita-ku, Okayama, Japan Sarah Alansari     Consortium for Translational Orthodontic Research, Orthodontic Department, College of Dentistry, New York University, New York, NY, USA Mani Alikhani     Consortium for Translational Orthodontic Research, Orthodontic Department, College of Dentistry, New York University, New York, NY, USA Mona Alikhani     Consortium for Translational Orthodontic Research, Orthodontic Department, College of Dentistry, New York University, New York, NY, USA Agnieszka Arthur, PhD     Bone and Cancer Laboratories, Department of Haematology, SA Pathology, Adelaide, SA, Australia Shylaja Arulkumar, MTech     Centre for Stem Cell Research (CSCR) (A unit of the Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru), Christian Medical College Campus, Vellore, India Silvia Baiguera, PhD     Advanced Center for Translational Regenerative Medicine (ACTREM), Karolinska Institutet, Stockholm, Sweden Alessandra Bianco, PhD     Department of Enterprise Engineering, Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome “Tor Vergata,” Rome, Italy Nabil F. Bissada, DDS, MSD     Department of Periodontics, Case Western Reserve University School of Dental Medicine, Cleveland, OH, USA Françoise Bleicher, PhD     Team Evo-Devo of vertebrate dentition, Institute of functional genomics of Lyon, UMRCNRS 5242, University Lyon 1 Faculty of Odontology, Lyon, France Jacqueline M. Bliley, MS     Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA Dieter D. Bosshardt, PhD     Robert K. Schenk Laboratory of Oral Histology, School of Dental Medicine, University of Bern, Bern, Switzerland Tatiana M. Botero, DDS, MS     Department of Cardiology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA Raquel Braga, DDS     University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, USA Kristen K. Briggs, PhD     Department of Bioengineering, UC San Diego, CA, USA Patricia J. Brooks, HBSc, MSc, DDS     Faculty of Dentistry, Schulich School of Medicine & Dentistry, University of Western Ontario, ON, Canada Kevin Cannon, BS     Department of Biological Sciences, and Center for Translational Cancer Research (CTCR), University of Delaware, Newark, DE, USA Florence Carrouel, PhD     Team Evo-Devo of vertebrate dentition, Institute of functional genomics of Lyon, UMRCNRS 5242, University Lyon 1 Faculty of Odontology, Lyon, France Miquella G. Chavez, PhD     Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, and Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA Ming-Te Cheng, MD, PhD     Taoyaun General Hospital, Taoyuan; School of Medicine, and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan George J. Christ, PhD     Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA Colin A. Cook     Laboratory for Craniofacial and Orthopaedic Tissue Engineering, Translational Tissue Engineering Center, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA Paul R. Cooper, BSc (Hons), PhD     School of Dentistry, University of Birmingham, Birmingham, United Kingdom Timothy C. Cox, PhD Division of Craniofacial Medicine, Department of Pediatrics, University of Washington Center for Developmental Biology & Regenerative Medicine, Seattle Children’s Research Institute; and Craniofacial Center, Seattle Children’s Hospital, Seattle, WA, USA, and Department of Anatomy & Developmental Biology, Monash University, Clayton, VIC, Australia Michael L. Cunningham, MD, PhD Division of Craniofacial Medicine, Department of Pediatrics, University of Washington Center for Developmental Biology & Regenerative Medicine, Seattle Children’s Research Institute; and Craniofacial Center, Seattle Children’s Hospital, Seattle, WA, USA Jesse Dashe, MD     Department of Surgery, University of California School of Medicine, La Jolla, CA, USA Ze’ev Davidovitch, DDS     Department of Orthodontics, Case Western Reserve University School of Dental Medicine, Cleveland, OH, and Department of Orthodontics, Harvard School of Dental Medicine, Cambridge, MA, USA Lindsay C. Davies, PhD     Wound Biology Group, Tissue Engineering and Reparative Dentistry, Cardiff Institute of Tissue Engineering and Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, United Kingdom Costantino Del Gaudio, PhD     Department of Enterprise Engineering, Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome “Tor Vergata,” Rome, Italy Thomas G.H. Diekwisch, DDS     The University of Illinois College of Dentistry, Department of Oral Biology, Brodie Laboratory, Chicago, IL, USA Anibal Diogenes, DDS, MS, PhD     Department of Endodontics, University of Texas Health Science Center at San Antonio, TX, USA Randall L. Duncan, PhD     Department of Biological Sciences, and Center for Translational Cancer Research (CTCR), University of Delaware, Newark, DE, USA Paul C. Edwards, DDS, MSc,     Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indianapolis, IN, USA Tarek El-Bialy, BDS, MSc, LLP, PhD, EMBA     Orthodontics and Biomedical Engineering Department, University of Alberta, Edmonton, Alberta, Canada Donald H. Enlow, PhD     Department of Orthodontics, Case Western Reserve University School of Dental Medicine, Cleveland, OH, USA Mary C. Farach-Carson, PhD     Biochemistry and Cell Biology, and Bioengineering, Rice University, Houston, TX, USA Jean-Christophe Farges, DDS, PhD     Team Evo-Devo of vertebrate dentition, Institute of functional genomics of Lyon, UMRCNRS 5242, University Lyon 1 Faculty of Odontology, Lyon, France Stephen E. Feinberg, DDS, MS, PhD     Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI, USA Hady Felfy, PhD     Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA Phillip N. Freeman, DDS, MD     Department of Oral and Maxillofacial Surgery, University of Texas School of Dentistry at Houston, Houston, TX,...